ABSTRACT

In the last seven years a large number of estrogen receptor variant mRNAs derived from alternative splicing of the primary transcript have been described. In most of these messengers one or several exons are skipped. Alternative splicing frequently occurs during the processing of many primary transcripts, but the coexistence of many different mature messenger RNAs derived from the same gene in the same cell as observed for the estrogen receptor gene (exon promiscuity) has been described in only a few cases. Cells that express the mature full-length transcript of the estrogen receptor gene nearly always express also at least some of the variant mRNAs. The subset of variants expressed in a single tissue or cell line, and the expression level of the single variant, undergo variations. Some variability of variant expression in human breast tumors in correlation to other tumor markers have also been described, and it has been suggested that the variants are involved in tumor progression from the estrogen dependent and antagonist responsive to the hormone independent and antagonist insensitive growth phase. However, the data available do not sustain this hypothesis. Translation of variant mRNAs of the estrogen receptor into protein has been described, although direct evidence of endogenous variant protein expression lacks for most variant messengers. The functional characterization of single variants has led to contrasting results as far as interference with the normal receptor function is concerned. The physiological role of ER variants and their contribution to tumor growth, if any, remain to be identified.